None listed
Conditions
Brief summary
The purpose of this study is to examine the safety, anti-cancer activity, and how the body metabolises a new medication called EO1001. Who is it for? You may be eligible for this study if you are aged 18 or over and have metastatic or advanced cancer. Study details All participants in this study will receive the active medication.. All participants will have a single dose of the medication to test how the body metabolises the drug. The drug is taken as an oral tablet, and the dose will depend on when the participant enrols in the study. About a week later, participants will start consuming the medication at the dose they started every day. Treatment will continue from this point, until those running the study decide to halt treatment, or the participant is unable to continue. As part of this study, participants will be required to undergo blood tests to assess safety and undergo scans to determine cancer status. It is hoped this research will demonstrate this medication is safe and effective in treating advanced cancer.
Interventions
Tier 1a and 1b (Dose Escalation):
Patients enrolled in the study will receive one oral dose of EO1001. Up to eight dose escalation cohorts are planned at the following incremental single-daily dose levels:
Cohort 1 = 2.5 mg q.d;
Cohort 2 = 10 mg q.d;
Cohort 3 = 20 mg q.d;
Cohort 4 = 30 mg q.d.;
Cohort 5 = 50 mg q.d.;
Cohort 6 = 70 mg q.d.;
Cohort 7 = 90 mg q.d.;
Cohort 8 = 120 mg q.d.;
Cohort 9 = 160 mg q.d..
All patients will start on Tier 1a, the dose at which they will be treated will depen
Tier 1a and 1b (Dose Escalation): Patients enrolled in the study will receive one oral dose of EO1001. Up to eight dose escalation cohorts are planned at the following incremental single-daily dose levels: Cohort 1 = 2.5 mg q.d; Cohort 2 = 10 mg q.d; Cohort 3 = 20 mg q.d; Cohort 4 = 30 mg q.d.; Cohort 5 = 50 mg q.d.; Cohort 6 = 70 mg q.d.; Cohort 7 = 90 mg q.d.; Cohort 8 = 120 mg q.d.; Cohort 9 = 160 mg q.d.. All patients will start on Tier 1a, the dose at which they will be treated will depend on which dose cohort they are allocated to. Cohort 1 patients will receive 2.5mg once daily, when the patient has received 28 days of treatment and the Safety Review Committee have cleared the dose, the next dose cohort will be open ie 10mg once daily and so only until the maximum tolerated dose is reached. Cycle 1: Patients will receive a single dose of oral EO1001 on day 1 and single dose pharmacokinetics will be performed at nominated time points for 7 days. Beginning on day 8, oral EO1001 will be administered once daily for 21 days. Multi-dose pharmacokinetics will be performed at the nominated time points. Cycles 2-6: Oral EO1001 will be administered once daily in continuous 28-day cycles for up to 20 weeks. Multi-dose pharmacokinetics will be performed at the nominated time points. Following Cycle 6, participants without DLT or disease progression may be offered continued treatment in an extension protocol upon recommendation of the principal investigator. Tier 2 (MTD Expansion): When the Safety Review Committee state that maximum tolerated dose (MTD) is reached additional patients will be recruited to the MTD dose. Oral EO1001 will be administered once daily in continuous 28 day cycles for up to 6 cycles (24 weeks). Multi-dose pharmacokinetics will be performed at the nominated time points. Following Cycle 6, participants without DLT or disease progression may be offered continued treatment in an extension protocol upon recommendation of the principal investigator Adherence to investigational product treatment will be monitored by the study coordinator by counting the tablets returned to the unit and reviewing the participant diary.
Sponsors
Senz Oncology Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Male or female >= 18 years of age participants with confirmed diagnosis of metastatic or advanced stage ErbB-1 (EGFR), ErbB-2 (HER2) and/or ERbB-4 (HER4) positive cancer who have relapsed after treatment with approved therapies and are unsuitable for further treatment with approved therapies or declined further treatment with approved therapies. • Participants must sign informed consent. • Participants must have measurable disease, defined as at least 1 unidimensional measurable lesion on an imaging scan as defined by RECIST 1.1. • Life expectancy of greater than 3 months. • Acceptable organ function, as evidenced by the following laboratory data during screening period: • Adequate hepatic function as defined by bilirubin less than or equal to 1.5 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN. Serum bilirubin must be less than or equal to 2.5 mg/dL when increase is clearly documented as due to Gilbert’s syndrome. • Adequate renal function, with serum creatinine less than or equal to 1.5 x ULN or MDRD greater than or equal to 60 mL/min (CKD EPI Creatinine Equation). o CNS metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement may be enrolled provided they are stable as shown by CT/MRI scan at least 4 weeks before screening without evidence of cerebral oedema. o Patients with CNS metastases requiring corticosteroids or anticonvulsants must be on a stable or declining dose for a minimum of 10 days prior to cycle 1 day 1 o Patients with leptomeningeal disease may be allowed in the study in agreement with sponsor and medical monitor.
Exclusion criteria
• Active infection requiring systemic treatment, defined as requiring antimicrobial, antifungal, or antiviral agents. • Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol. • Untreated or symptomatic brain metastases. Participants with treated or untreated brain metastases are NOT eligible if there has been a change in brain disease status in the 8 weeks prior to screening. This includes evidence of radiological progression, clinical decline and increasing steroid dose. • Current or recent (within 10 days of Cycle 1 Day 1) use of full dose oral or parenteral anticoagulants or other thrombolytic agents for therapeutic (as opposed to prophylactic) purposes, clinically serious non-healing wounds, or incompletely healed bone fracture. • Participants on > 2mg dexamethasone (or steroid equivalent). • Ventriculoperitoneal (VP) shunts. • Renal compromised or renal failure. • Hepatic compromised or hepatic failure. • Bullous and exfoliative skin disorders. • Interstitial lung disease (ILD) • Participants with adequate cardiac function ( less than or equal to NYHA class II) or normal cardiac function with left ventricular ejection fraction (LVEF) less than or equal to 50% at screening. • Anticancer therapy within 4 weeks, or a minimum of 5 half-lives whichever is longer. • Pregnancy or breast-feeding. • Inability to swallow oral medications or having malabsorption syndrome. • Unresolved adverse reactions to prior treatments NCI CTCAEv5 > Grade 1. • Any serious medical or psychiatric conditions which the Investigator feels may interfere with the patient’s ability to give informed consent or participate in the procedures or evaluations of the study. • Abnormal coagulation not corrected by plasma infusion (APTT > ULN or INR> 1.2). • Participants of childbearing potential who do not agree to use at least 2 effective contraceptive methods throughout the study and for 6 months following completion of treatment. • Female participants who are pregnant or lactating. • Unstable angina or acute myocardial infarction less than or equal to 6 months prior to starting study treatment. • Baseline QTc greater than or equal to 470 msec • Cardiomyopathy. • Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Outcome results
None listed